Clinical and Genetic Analysis in Pediatric Patients with Multiple Sclerosis and Related Conditions: Focus on DR Genes of the Major Histocompatibility Complex

Aigerim Galym1, Nazgul Akhmetova1, Madina Zhaksybek1, Svetlana Safina1, Margaritha N. Boldyreva2, Farida K. Rakhimbekova3, Zhannat R. Idrissova1, *
1 Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
2 Institute of Immunology Academy of Medical Science of Russia, Moscow, Russian Federation
3 Satpaev University, Almaty, Kazakhstan

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© 2022 Galym et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan; E-mail:



There are several diseases recognized as variants of MS: post-infectious acute disseminated encephalitis, multiple sclerosis (MS), Rasmussen leukoencephalitis and Schilder's leukoencephalitis and related, but separate neuroimmune condition – Neuromyelitis Devic’s. In Kazakhstan diagnosis of such diseases was rare and immune modified treatment was only admitted after the age of 18. Clinical and immunogenetic study of MS spectrum diseases in Kazakhstan would allow to justify early targeted treatment.


The aim of the study was to investigate genes of the main complex of human histocompatibility (MHC) associated with diseases of MS spectrum in Kazakhstani population.


Complex clinical, neuroimaging and immunogenetic studies were performed in 34 children (24 girls, 10 boys) aged 4 to 18 years. 21 children were diagnosed with MS (11 Kazakh origin and 10 – Russian; 4 boys, 17 girls), 7 with leucoencephalitis (all Kazakh, 5 boys, 2 girls) and 6 with Devic neuromyelitis optica (all Kazakh, 1 boy, 5 girls). Genotyping of HLA DRB1, DQA1, DQB1 genes was performed for all patients.


MS group was characterized by classical relapsing-remitting MS. Predominant haplotype as a linkage complex was DRB1*15:01~DQA1*01:02~DQB1*06:02 in 20 (47.6%) of 42 DR-alleles, in 16 (76.2%) patients. MS relative risk (RR) was 13,36 for ethnic Kazakhs and RR=5,55 in Russians.

Leukoencephalitis had 7 children, with 28.6% mortality rate. The haplotype DRB1*15:01~DQA1*01:02~DQB1*06:02 as a linkage complex was detected 3 patients (4 alleles), RR=5,88.

Devic’s neuromyelitis optica (NMO) clinical course was characterized by fast and prolonged progression. There was predominance of DRB1*14 allele with RR=3,38.


Summarizing, in the Kazakh population the haplotype DRB1*15:01∼DQA1*01:02∼DQB1*06:02 as a linkage complex was associated with prediction to MS and leukoencephalitis, but not to Devic’s NMO. Our study highlights the importance of awareness of MS and related disorders diagnosis which allows to implement early admission of disease-modified treatment in pediatric MS in Kazakhstan.

Keywords: Neuro-immune diseases, Multiple sclerosis, Children, Major histocompatibility complex, Aquaporin, DRB, Genotyping.